At the end of the initial, three-year trial, women taking only calcium and vitamin D showed a significant decrease in 1/3 radius bone mineral density (BMD) and were offered to enroll in a trial extension, Dr. Brown said. Two thousand two hundred and seven women, most older than 65 years old, took 60 mg of denosumab every six months. After three years of treatment, researchers found that participants’ BMD returned to baseline and then increased 1.5% after five years.
Wrist fracture rates also dropped significantly once these women added denosumab, Dr. Brown said. In the original three-year trial, the placebo group’s wrist fracture rate increased by 1.02%. After three years of the denosumab extension, the rate dropped to 0.96%, and at years four and five, it dropped to 0.58%. A subset of participants with femoral neck T-scores of ≤2.5, “a very well-known risk factor for fracture, saw an almost 80% reduction in the occurrence of wrist fracture,” Dr. Brown said.
Autotaxin’s Role in Fibrosis
Although no effective treatments currently exist for systemic sclerosis (SSc), new research on autotaxin, a key mediator of the lipid lysophosphatidic acid (LPA), may offer hope, said Flavia V. Castelino, MD, assistant professor of medicine at Harvard Medical School in Boston.
Autotaxin is highly expressed in the skin of SSc patients, along with high levels of IL-6, she said. LPA induction of autotaxin requires IL-6, and this loop leads to fibroblast formation, subsequent extracellular matrix deposition and collagen accumulation in these patients, she said.
Dr. Castelino’s team studied autotaxin’s role in localized LPA production and SSc fibrosis. Mice received four subcutaneous injections of bleomycin over 28 days, and they expressed autotaxin after three days. Using a novel autotaxin inhibitor called PAT-048, they found that the drug abrogated bleomycin-induced dermal fibrosis and also reduced hydroxyproline content. The drug also attenuated IL-6 production in the skin of these mice, she said. The LPA-autotaxin-IL-6 loop is a potential target for developing new SSc therapies, she said.
Post-Transplant Mortality
Many transplant programs are reluctant to offer lungs to adults with SSc due to concerns about extrapulmonary involvement that may affect their survival. However, according to a retrospective cohort study published in 2014, adults with SSc had one-year mortality risk that was comparable to patients with pulmonary arterial hypertension (PAH), a widely accepted indication for lung transplantation, said Elana J. Bernstein, MD, MSc, instructor at Columbia University College of Physicians and Surgeons in New York City.
